Abstract
Abstract: :
Purpose: Levels of histamine, the primary mediator in allergy, can provide a direct measure of mast cell degranulation, but can be difficult to measure. This is the first study to evaluate an antiallergy eyedrop on mast cell mediators via the release of histamine, cellular infiltrate and upregulation of ICAM, and to correlate it with clinical signs and symptoms in the human eye. Methods: This was a double-masked, randomized, contralaterally controlled, clinical study utilizing a modified conjunctival allergen challenge (CAC) model. Ten patients received CAC with increasing doses of allergen to obtain a significant bilateral allergic response and to induce mast cell degranulation to attract lymphocytes and leukocytes. Two weeks later, patients were re-challenged to confirm the allergic response. Patients began treatment in one eye with olopatadine (Patanol-approved for BID dosing) and the contralateral eye with placebo BID for 5 days prior to Visit 3. At Visit 3, patients received a CAC 15 minutes following the final dose. Clinical signs and symptoms were recorded 5, 10, 20, 30 min and 5 hrs after CAC. The 5 hr time was selected based on previous studies in the CAC in untreated patients showing it as the peak effect of mast cell chemotactic agents and cellular infiltrate. The following parameters were evaluated: 1) tear cytology at 30 min and 5 hrs; 2) tear histamine before and 5 min after challenge (RIA); 3) ICAM-1 expression by immunocytochemistry on conjunctival epithelial cells via impression cytology before, 30 min and 5 hrs after CAC. Results: Itching and hyperemia were significantly (p<0.01) reduced by olopatadine compared to placebo at all time points. Compared to placebo, olopatadine significantly reduced number of neutrophils (p=0.015) and total number of cells (p=0.015) at 30 min, and number of eosinophils (p=0.0002), neutrophils (p=0.003), lymphocytes (p=0.01) and total number of cells (p=0.001) at 5 hr post-challenge. Histamine tear levels were dramatically lower after challenge in olopatadine treated eyes compared to placebo (7±8 nM/L vs 22.4±12 nM/L, p=0.001). As well, ICAM-1 expression on epithelial cells was significantly reduced in olopatadine treated eyes compared to placebo, both at 30 min and 5 hrs. Conclusions: Olopatadine reduced the release and effect of mast cell derived mediators in the human eye. This is the first study correlating clinical effects and the indices of mast cell stabilizing properties, including decreased histamine levels, for a therapeutic agent in ocular allergic subjects.
Keywords: clinical (human) or epidemiologic studies: tre • conjunctivitis • cytology